Altered glycosylation of α-dystroglycan in neurons of Fukuyama congenital muscular dystrophy brains

Abstract

To test the hypothesis that the disruption of fukutin protein produces the brain pathology through hypoglycosylation of α-dystroglycan (α-DG), we immunostained Fukuyama congenital muscular dystrophy (FCMD) brains with an antibody that recognizes the polysaccharide epitope of α-DG. Immunoreactivity of the glia-limitans along the cortical surface, as well as that of the glial endfeet around vessel walls, was preserved in the FCMD cerebrum. However, fragmentation of the immunostained glia-limitans was noted in association with parenchymal protrusion and gyral fusion. In the FCMD cerebellum, this fragmentation of α-DG labeling was limited to the area of micropolygyria, and immunostaining at the glia-limitans and vessel walls was comparable to that of the control brains, in structurally normal areas. In the hippocampus, neurons of the dentate gyrus and corpus ammonis were immunopositive for α-DG in control subjects, but this staining was markedly decreased in FCMD brains. In contrast, immunolabeling of blood vessels and the glia-limitans was preserved in this region. Fukutin antisera clearly labeled hippocampal neurons in control brains, while this labeling was decreased in FCMD brains. Thus, hypoglycosylation of α-DG was evident in neurons, but not in the glial cell population of FCMD brains. This suggests that the mechanism of α-DG glycosylation may differ between neurons and glial cells, and that a fukutin gene defect may result in functional disruption through hypoglycosylation of both neuronal and glial α-DG.